Interactions of complement proteins C1q and factor H with lipid A and Escherichia coli: further evidence that factor H regulates the classical complement pathway.
10.1007/s13238-011-1029-y
- Author:
Lee Aun TAN
1
;
Andrew C YANG
;
Uday KISHORE
;
Robert B SIM
Author Information
1. Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX13QU, UK.
- Publication Type:Journal Article
- MeSH:
Binding, Competitive;
immunology;
Complement Activation;
immunology;
Complement C1q;
chemistry;
immunology;
metabolism;
Complement C4b;
analysis;
Complement Factor H;
chemistry;
immunology;
metabolism;
Complement Pathway, Classical;
immunology;
Escherichia coli;
immunology;
metabolism;
Humans;
Iodine Radioisotopes;
Isotope Labeling;
Lipid A;
immunology;
metabolism;
Liposomes;
immunology;
metabolism;
Protein Binding;
immunology;
Recombinant Proteins;
chemistry;
immunology;
metabolism;
Substrate Specificity
- From:
Protein & Cell
2011;2(4):320-332
- CountryChina
- Language:English
-
Abstract:
Proteins of the complement system are known to interact with many charged substances. We recently characterized binding of C1q and factor H to immobilized and liposomal anionic phospholipids. Factor H inhibited C1q binding to anionic phospholipids, suggesting a role for factor H in regulating activation of the complement classical pathway by anionic phospholipids. To extend this finding, we examined interactions of C1q and factor H with lipid A, a well-characterized activator of the classical pathway. We report that C1q and factor H both bind to immobilized lipid A, lipid A liposomes and intact Escherichia coli TG1. Factor H competes with C1q for binding to these targets. Furthermore, increasing the factor H: C1q molar ratio in serum diminished C4b fixation, indicating that factor H diminishes classical pathway activation. The recombinant forms of the Cterminal, globular heads of C1q A, B and C chains bound to lipid A and E. coli in a manner qualitatively similar to native C1q, confirming that C1q interacts with these targets via its globular head region. These observations reinforce our proposal that factor H has an additional complement regulatory role of down-regulating classical pathway activation in response to certain targets. This is distinct from its role as an alternative pathway down-regulator. We suggest that under physiological conditions, factor H may serve as a downregulator of bacterially-driven inflammatory responses, thereby fine-tuning and balancing the inflammatory response in infections with Gram-negative bacteria.